Contributions from the left PMd and the SMA during sequence retrieval as determined by depth of training.

The dorsal premotor cortex (PMd) and the supplementary motor area (SMA) are critical for the acquisition and expression of sequential behavior, but little is known regarding how these regions are recruited when we must simultaneously acquire multiple sequences under different amounts of training. We hypothesized that these regions contribute to the retrieval of sequences at different familiarity levels, with the left PMd supporting sequences of moderate familiarity and the SMA supporting sequences of greater familiarity. Double-pulse transcranial magnetic stimulation (TMS) was applied during the retrieval of six sequences previously learned under three different amounts of exposure during 30 days of training using a discrete sequence production task. TMS led to a significant interaction of sequence error between depth of training and stimulation location. Stimulation of the left PMd increased error during moderate sequence retrieval, whereas stimulation of the SMA increased error during the retrieval of both moderately and extensively trained sequences. The lack of a double dissociation fails to support a direct correspondence between brain region and putative behavioral learning stage. Instead, the interaction suggests that SMA and PMd support the expression of sequences over different, albeit overlapping, time scales. Separate analysis of sequence initiation time did not demonstrate any significant difference between moderately and extensively trained sequences. Instead, stimulation to either region quickened sequence initiation for these sequences, but not for those sequences with poor retrieval performance. This supports the general role of these premotor regions in the maintenance of specific sequence knowledge prior to movement onset.